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Article ; Online: Circulating Microvesicles in Convalescent Ischemic Stroke Patients: A Contributor to High-On-Treatment Residual Platelet Reactivity?

Schrick, Diana / Molnár, Tihamér / Tőkés-Füzesi, Margit / Molnár, Abigél / Ezer, Erzsébet

Frontiers in bioscience (Landmark edition)

2022 Volume 27, Issue 5, Page(s) 158

Abstract: Introduction: Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next ... ...

Abstract	Introduction: Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next vascular event. Patients with high-on-treatment platelet reactivity (HTPR) had a significantly higher risk for ischemic stroke. Here, we aimed to explore associations among circulating microparticles and responsivness to antiplatelet (clopidogrel) therapy. Methods: A total of 18 patients on clopidogrel therapy due to secondary stroke prevention were rospectively recruited into this study. Twenty age-matched healthy subjects served as controls. Flow cytometric measurements of microparicles (MVs) and data analysis were performed on Beckman-Coulter FC-500 cytometer with CXP software. Besides, platelet aggregometry data were revealed. Both measurements were performed in whole blood and from the lower and upper blood fractions separated after 1-hour gravity sedimentation by the analogy with erythrocyte sedimentation rate. Results: The total number of circulating MVs, and particularly the platelet derived CD42+ and PAC-1+ were significantly higher in post-stroke patients ( Conclusions: Circulating MVs may allow to monitor the response to antiplatelet therapy in post-stroke patients. In addition, the link between platelet derived MVs and neutrophil granulocytes might become therapeutic targets in the future.
MeSH term(s)	Blood Platelets/physiology ; Cell-Derived Microparticles ; Clopidogrel/therapeutic use ; Humans ; Ischemic Stroke ; Platelet Aggregation Inhibitors/therapeutic use ; Stroke/drug therapy
Chemical Substances	Platelet Aggregation Inhibitors ; Clopidogrel (A74586SNO7)
Language	English
Publishing date	2022-05-30
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2705158
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Article ; Online: Gravity sedimentation reveals functionally and morphologically different platelets in human blood.

Ezer, Erzsébet / Schrick, Diana / Tőkés-Füzesi, Margit / Papp, István / Réger, Barbara / Molnár, Abigél / Ábrahám, Hajnalka / Koller, Akos / Hársfalvi, Jolán / Kellermayer, Miklós / Molnár, Tihamér

Platelets

2024 Volume 35, Issue 1, Page(s) 2298341

Abstract: In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte sedimentation (ESR), it can be expressed with the platelet antisedimentation rate (PAR), which ...

Abstract	In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte sedimentation (ESR), it can be expressed with the platelet antisedimentation rate (PAR), which quantitates the difference in platelet count between the upper and lower halves of the blood column after 1 h of 1 g sedimentation. Venous blood samples from 21 healthy subjects were analyzed for PAR. After a 1-h sedimentation, the upper and lower fractions of blood samples were analyzed for platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and high-fluorescence IPF (H-IPF). The mechanisms behind platelet flotation were explored by further partitioning of the blood column, time-dependent measurements of platelet count and comparison with ESR. The structure and function of the platelets were assessed by electron microscopy (EM) and atomic force microscopy (AFM), and platelet aggregometry, respectively. Platelet antisedimentation is driven by density differences and facilitated by a size-exclusion mechanism caused by progressive erythrocyte sedimentation. The area under the curve (AUC) of the whole blood adenosine diphosphate (ADP) aggregation curves showed significant differences between the upper and lower samples (
MeSH term(s)	Humans ; Blood Platelets ; Platelet Count ; Erythrocytes ; Mean Platelet Volume ; Adenosine Diphosphate
Chemical Substances	Adenosine Diphosphate (61D2G4IYVH)
Language	English
Publishing date	2024-01-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1034283-7
ISSN	1369-1635 ; 0953-7104
ISSN (online)	1369-1635
ISSN	0953-7104
DOI	10.1080/09537104.2023.2298341
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Article ; Online: Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.

Molnar, Tihamer / Lehoczki, Andrea / Fekete, Monika / Varnai, Reka / Zavori, Laszlo / Erdo-Bonyar, Szabina / Simon, Diana / Berki, Tímea / Csecsei, Peter / Ezer, Erzsebet

GeroScience

2024

Abstract: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of ... ...

Abstract	The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition.
Language	English
Publishing date	2024-04-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-024-01165-5
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Article: Novel Predictors of Future Vascular Events in Post-stroke Patients-A Pilot Study.

Schrick, Diana / Ezer, Erzsebet / Tokes-Fuzesi, Margit / Szapary, Laszlo / Molnar, Tihamer

Frontiers in neurology

2021 Volume 12, Page(s) 666994

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2021-06-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.666994
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Article: General Anesthesia-Related Drop in Diastolic Blood Pressure May Impact the Long-Term Outcome in Stroke Patients Undergoing Thrombectomy.

Abada, Alan / Csecsei, Peter / Ezer, Erzsebet / Lenzser, Gabor / Hegyi, Peter / Szolics, Alex / Merei, Akos / Szentesi, Andrea / Molnar, Tihamer

Journal of clinical medicine

2022 Volume 11, Issue 11

Abstract: Background: Several factors affect the efficacy of endovascular thrombectomy (EVT); however, the anesthesia-related factors have not been fully explored. We aimed to identify independent predictors of outcome by analyzing procedural factors based on a ... ...

Abstract	Background: Several factors affect the efficacy of endovascular thrombectomy (EVT); however, the anesthesia-related factors have not been fully explored. We aimed to identify independent predictors of outcome by analyzing procedural factors based on a multicentric stroke registry. Methods: Data of consecutive patients with acute ischemic stroke (AIS) were extracted from the prospective STAY ALIVE stroke registry. Demographic, clinical, and periprocedural factors including hemodynamic values were analyzed in patients undergoing thrombectomy with either general anesthesia (GA) or conscious sedation (CS). Independent predictors of outcome both at 30 and 90 days based on the modified Rankin Scale (mRS: 0−2 as favorable outcome) were also explored. Results: A total of 199 patients (GA: 76 (38%) vs. CS: 117 (59%); in addition, six patients were converted from CS to GA) were included. The minimum value of systolic, diastolic, and mean arterial pressure was significantly lower in the GA compared to the CS group, and GA was associated with a longer onset to EVT time and a higher drop in all hemodynamic variables (all, p < 0.001). A higher drop in diastolic blood pressure (DBP) was even independently associated with a poor 90-day outcome (p = 0.024). Conclusion: A GA-related drop in DBP may independently predict a poor long-term outcome in stroke patients undergoing thrombectomy.
Language	English
Publishing date	2022-05-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11112997
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Article ; Online: A novel approach of platelet function test for prediction of attenuated response to clopidogrel.

Ezer, Erzsebet / Schrick, Diana / Tőkés-Füzesi, Margit / Szapary, Laszlo / Bogar, Lajos / Molnar, Tihamer

Clinical hemorheology and microcirculation

2019 Volume 73, Issue 2, Page(s) 359–369

Abstract: Background: Elevated mean platelet volume (MPV) and immature platelet fraction (IPF) are predictive for vascular risk. Both can be associated with residual platelet reactivity. We aimed to explore associations among platelet characteristics and ... ...

Abstract	Background: Elevated mean platelet volume (MPV) and immature platelet fraction (IPF) are predictive for vascular risk. Both can be associated with residual platelet reactivity. We aimed to explore associations among platelet characteristics and responder status in stroke patients on clopidogrel. Methods: Blood samples from 46 patients and 15 healthy subjects were analyzed for platelet count, MPV, IPF, large cell ratio (LCR) and high-fluorsecent immature platelet fraction (H-IPF). As a novelty, not only whole blood, but upper and lower half blood samples after 1-hour gravity sedimentation were analyzed. Platelet aggregometry was used for the whole blood and separated samples to explore area under the curve (AUC) in patients and controls. Results: The AUC of the whole blood showed significant differences compared to the upper and lower samples separated after 1-hour sedimentation in patients and controls (p < 0.001 and p = 0.005 respectively). Remarkably, AUC measured in the upper samples in 59% of patients on clopidogrel were exceeding the therapeutic range suggesting that ascending platelets exert aggregation in the presence of ADP. This observation was associated with increased MPV and LCR in the upper samples (both p = 0.04). Patients on clopidogrel were characterized as responders and non-responders and the percentage of H-IPF was significantly higher among non-responders compared to controls in the upper samples (p = 0.04). Conclusions: The modified platelet function test may help to stratify patients with high residual platelet reactivity.
MeSH term(s)	Aged ; Blood Platelets/physiology ; Clopidogrel/pharmacology ; Female ; Humans ; Male ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Platelet Function Tests/methods
Chemical Substances	Platelet Aggregation Inhibitors ; Clopidogrel (A74586SNO7)
Language	English
Publishing date	2019-05-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1381750-4
ISSN	1875-8622 ; 1386-0291
ISSN (online)	1875-8622
ISSN	1386-0291
DOI	10.3233/CH-190580
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Zs.A 1623: Show issues

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Article ; Online: Relationship between Cardiac Troponin and Thrombo-Inflammatory Molecules in Prediction of Outcome after Acute Ischemic Stroke.

Csecsei, Peter / Pusch, Gabriella / Ezer, Erzsebet / Berki, Timea / Szapary, Laszlo / Illes, Zsolt / Molnar, Tihamer

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2018 Volume 27, Issue 4, Page(s) 951–956

Abstract: Background: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers.!# ...

Abstract	Background: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. Methods: Thirty-five patients with first-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after stroke. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, 24 hours later, and at discharge. Results: Concentration of MCP-1 at 6 hours was higher in the serum of patients with worsened NIHSS by 24 hours (P = .009). Concentration of hs-cTnT at both 6 and 24 hours was higher, if NIHSS worsened by discharge (P = .026 and P = .001). A cutoff value for hs-cTnT measured at T24 greater than or equal to 9.4 predicted worsened NIHSS on discharge with a sensitivity of 81% and a specificity of 74% (area: .808, P = .002). Concentration of hs-cTnT at both 6 and 24 hours was also higher in nonsurvivors compared with survivors (P = .03, respectively), and correlated with (1) tPA levels at 6 hours (P = .001 and P = .002, respectively); (2) MCP-1 concentration at 6 hours (P = .01 and P = .015, respectively); and increased hsCRP levels at 72 hours (P = .01, respectively). Concentration of hs-cTnT at 24 hours was an independent predictor of worsened NIHSS at discharge (odds ratio: 1.58, 95% confidence interval: 1.063-2.370, P = .024). Conclusions: Elevated concentration of hs-cTnT measured 24 hours after AIS is an independent predictor of progressing neurologic deficit in patients without apparent myocardial damage, and also correlates with acute elevation of tPA and MCP-1.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Brain Ischemia/blood ; Brain Ischemia/diagnosis ; Brain Ischemia/mortality ; Brain Ischemia/therapy ; Chemokine CCL2/blood ; Chi-Square Distribution ; Disability Evaluation ; Female ; Humans ; Inflammation Mediators/blood ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Risk Factors ; Stroke/blood ; Stroke/diagnosis ; Stroke/mortality ; Stroke/therapy ; Time Factors ; Tissue Plasminogen Activator/blood ; Troponin T/blood ; Up-Regulation
Chemical Substances	Biomarkers ; CCL2 protein, human ; Chemokine CCL2 ; Inflammation Mediators ; Troponin T ; Tissue Plasminogen Activator (EC 3.4.21.68)
Language	English
Publishing date	2018-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2017.10.040
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Article: Magyarországi intenzív osztályok szervdonációval kapcsolatos személyi és tárgyi feltételei.

Mihály, Sándor / Egyed-Varga, Anita / Holtzinger, Emese / Kara, Kristóf / Ezer, Erzsébet / Szedlák, Balázs / Smudla, Anikó / Nacsa, János / Matusovits, Andrea

Orvosi hetilap

2018 Volume 159, Issue 33, Page(s) 1360–1367

Abstract: Introduction: At the end of 2016, the number of patients on the domestic transplant waiting list was twice as much as the number of the organ transplantations accomplished that year. The institutional prerequisites for functional organ donation programs ...

Title translation	Personnel and material conditions of the Hungarian intensive care units dealing with organ donation.
Abstract	Introduction: At the end of 2016, the number of patients on the domestic transplant waiting list was twice as much as the number of the organ transplantations accomplished that year. The institutional prerequisites for functional organ donation programs are the sufficient number of personnel and the adequate material conditions to be provided in relation to the needs. Aim: The goal of the current study was to evaluate the professional environment in Hungary. Method: The Organ Coordination Office at the Hungarian National Blood Transfusion Service compiled a questionnaire survey on the personnel and material conditions of the intensive care units (ICUs) in Hungary in regards to organ donations. The survey applied an online questionnaire including 43 questions. In addition to the number of beds and employees, we investigated the tools needed for the legal and the medical diagnosis of brain death as well as the accessibility of examinations on the donor information form. The data collection spanned from 12 December 2016 to 30 June 2017. Results: 59 intensive care units completed the questionnaire; the investigation involved 640 hospital beds, 816 physicians and 1252 nurses. In the daytime shift, 0.25 doctors and 0.41 nurses work on a patient bed at an average, while in the night shift, the figures are 0.11 and 0.33, respectively. 51.7% of the doctors are registered to access the National Non-Donor Registry, and brain death diagnosis committee is available in 83% of the hospitals. Among the medical imaging methods (cranial, abdominal-thoracic), CT scan in 71-73%, abdominal ultrasound in 75%, transthoracic echocardiograpy (TTE) in 37%, transoesophageal echocardiography (TEE) in 4%, bronchoscopy in 49%, coronarography in 19% are non-stop available, with instant interpretation in 75% of the cases. Transcranial Doppler (TCD) in 30%, four-vessel angiography in 45% and SPECT in 14% of the cases are available. More than 90% of the laboratory examinations on the donor information form are available 24 hours a day. Conclusion: The number of doctors and nurses did not change compared to our 2008 survey (0.18 doctors, 0.37 nurses/ICU beds in 2008), but the care of potential donors needs more resources and time. The standby availability of personnel and material conditions is a prerequisite for organ donation programs in order to save lives. Orv Hetil. 2018; 159(33): 1360-1367.
MeSH term(s)	Attitude of Health Personnel ; Female ; Humans ; Hungary ; Intensive Care Units/organization & administration ; Male ; Medical Staff, Hospital/statistics & numerical data ; Nursing Staff, Hospital/statistics & numerical data ; Patient Care Team/organization & administration ; Tissue Donors/supply & distribution ; Tissue and Organ Procurement/organization & administration
Language	Hungarian
Publishing date	2018-08-12
Publishing country	Hungary
Document type	Journal Article
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/650.2018.31139
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Article: Baleseti agysérültek ellátásának irányelvei - 2017.

Büki, András / Barzó, Pál / Demeter, Béla / Kanizsai, Péter / Ezer, Erzsébet / Tóth, Péter / Horváth, Péter / Varga, Csaba

Ideggyogyaszati szemle

2018 Volume 70, Issue 7-8, Page(s) 223–245

Abstract: Traumatic brain injury (TBI) is recognized to be the main cause of death and disability in the first four decades representing a major socio-economical problem worldwide. Recent communications revealed a particularly worrying image about the quality of ... ...

Title translation	Guidelines for the treatment of traumatic brain injury - 2017.
Abstract	Traumatic brain injury (TBI) is recognized to be the main cause of death and disability in the first four decades representing a major socio-economical problem worldwide. Recent communications revealed a particularly worrying image about the quality of care for TBI in Hungary. For any improvement a systematic approach characterized by utilization of scientific evidence based guidelines forming the basis for close monitoring of the actual care are considered a prerequisite. In Hungary the first evidence based guidelines in the field of TBI have been issued by the National Society for Anesthesiology and Intensive Care more than two decades ago followed by joint guidelines of the Hungarian Neurosurgical Society and the Hungarian College of Neurosurgeons. These publications were primarily based on the work of the European Brain Injury Consortium as well as guidelines issued by the Brain Trauma Foundation. Recent renewal of the latter and a need to refresh the outdated national guidelines was met by a call from regulatory authorities to issue the updated version of the Hungarian TBI-guidelines. The present review is aimed to briefly summarize the most fundamental elements of the national head injury guidelines that would hopefully be officially issued in a far more detailed format soon.
MeSH term(s)	Brain Injuries, Traumatic/therapy ; Evidence-Based Medicine ; Humans ; Hungary ; Practice Guidelines as Topic
Language	Hungarian
Publishing date	2018-06-05
Publishing country	Hungary
Document type	Journal Article ; Review
ZDB-ID	2240317-6
ISSN	0019-1442
ISSN	0019-1442
DOI	10.18071/isz.70.0223
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Article ; Online: Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling: Pathomechanisms, perspectives, and therapeutic implications.

Toth, Peter / Szarka, Nikolett / Farkas, Eszter / Ezer, Erzsebet / Czeiter, Endre / Amrein, Krisztina / Ungvari, Zoltan / Hartings, Jed A / Buki, Andras / Koller, Akos

American journal of physiology. Heart and circulatory physiology

2016 Volume 311, Issue 5, Page(s) H1118–H1131

Abstract: Traumatic brain injury (TBI) is a major health problem worldwide. In addition to its high mortality (35-40%), survivors are left with cognitive, behavioral, and communicative disabilities. While little can be done to reverse initial primary brain damage ... ...

Abstract	Traumatic brain injury (TBI) is a major health problem worldwide. In addition to its high mortality (35-40%), survivors are left with cognitive, behavioral, and communicative disabilities. While little can be done to reverse initial primary brain damage caused by trauma, the secondary injury of cerebral tissue due to cerebromicrovascular alterations and dysregulation of cerebral blood flow (CBF) is potentially preventable. This review focuses on functional, cellular, and molecular changes of autoregulatory function of CBF (with special focus on cerebrovascular myogenic response) that occur in cerebral circulation after TBI and explores the links between autoregulatory dysfunction, impaired myogenic response, microvascular impairment, and the development of secondary brain damage. We further provide a synthesized translational view of molecular and cellular mechanisms involved in cortical spreading depolarization-related neurovascular dysfunction, which could be targeted for the prevention or amelioration of TBI-induced secondary brain damage.
MeSH term(s)	Animals ; Brain Edema/physiopathology ; Brain Injuries, Traumatic/physiopathology ; Brain Ischemia/physiopathology ; Cerebral Arteries/physiopathology ; Cerebrovascular Circulation/physiology ; Cortical Spreading Depression/physiology ; Homeostasis ; Humans ; Intracranial Hypertension/physiopathology ; Microcirculation/physiology ; Neurovascular Coupling/physiology
Language	English
Publishing date	2016-09-09
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00267.2016
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